Recipient mice pretreated with TL1A-Ig+IL-2_LD before aHSCT enable GVL responses concomitant with GVHD amelioration. B6 (donor) → BALB/c (recipient) aHSCT with and without recipient TL1A-Ig+IL-2_LD pretreatment was performed. All groups received 5 × 10³ BALB/c-MLL-AF9^GFP cells (IV) at the time of aHSCT, (n = 9-13 mice per group). (A) Overall survival. No animals survived in the BM-only group vs >85% for the (BM + T cells) and (BM + T cells with recipient treatment) groups (n = 5). (B) BALB/c-MLL-AF9^GFP cell frequency in the PB at 3, 4, and 5 weeks after aHSCT. Treg expansion in the recipient group enabled a GVL response against BALB/c-MLL-AF9^GFP cells that was as effective as the response in untreated recipients (BM + T cells) denoted by minimal detection of GFP expression. (C) Representative photographs of mice from each group at 4 weeks after aHSCT. (D-G) BALB/c-MLL-AF9^GFP frequency in hematopoietic compartments, that is, the BM (D); and nonhematopoietic compartments, that is, the liver (E), uterus and ovaries (F), and spinal cord (G), at days 28 and 42 after aHSCT.